Stroke is a major cause of long-term disability in the United States. However, recovery of some of the lost motor functions can occur months to years after the original injury. As such, investigations into the underlying neural elements responsible for the motor recovery are of critical importance. Insights into the substrates for motor recovery have come from previous functional imaging, neurophysiological and neuroanatomical studies. Importantly, these studies have shown that spared motor areas located in the same hemisphere as the injury undergo dramatic changes in metabolism, neurophysiology and neuroanatomical connections and may contribute to the motor recovery process. However, we are still lacking in our understanding of the temporal characteristics and initial emergence of these reorganizations within these spared motor areas. As such, this lack of understanding may negatively affect future studies aimed at therapeutic interventions as the interventions may be employed at improper periods after the injury. Therefore, the long-term objectives for this proposal are to: 1) generalize previous neuroplasticity found in the ventral premotor cortex and supplementary motor area to the spared dorsal premotor cortex;2) identify the key time points when neuroplastic responses emerge and peak in both ventral and dorsal premotor cortices;3) examine plastic changes in motor output from the premotor cortex following M1 damage in the form of electromyograph changes;4) investigate the effect that rehabilitation of the affected arm has on neuroplastic responses in the premotor cortex. The findings generated from the above objectives may have a broad impact in the field of motor recovery following stroke and other brain injuries that affect motor performance. In particular, therapeutic interventions may be designed and employed to enhance the inherent ability of the cerebral cortex to adapt and reorganize in response to injury. Importantly, this study will help delineate key time-frames of peak neuroplasticity and enable clinicians and therapists to design and implement strategies to harness and expand upon this neuroplasticity and thereby increase the levels of motor recovery for brain injured patients. PUBLIC HEALTH RELEVANCE: This proposal is aimed at investigating the underlying neuroanatomical and neurophysiological substrates implicated in motor recovery following stroke and the effect that rehabilitation will have on these substrates. Specifically, this proposal postulates plastic changes to cortical connections, body representations and EMG properties within and from the premotor cortex in nonhumans primates following primary motor cortex damage. In addition, this proposal focuses on delineating a timeframe of peak plastic changes when rehabilitative efforts can be directed toward. As approximately 795,000 people will suffer a stroke per year and will have residual motor deficits, this proposal will have a dramatic impact on current and future studies designed to enhance motor recovery following stroke.